Research Article
GDF-15 and Hepcidin Levels in Nonanemic Patients with
Impaired Glucose Tolerance
Mehmet Muhittin Yalcin,
1
Alev Eroglu Altinova,
1
Mujde Akturk,
1
Ozlem Gulbahar,
2
Emre Arslan,
1
Damla Ors Sendogan,
3
Ilhan Yetkin,
1
and Fusun Balos Toruner
1
1
Department of Endocrinology and Metabolism, Gazi University Faculty of Medicine, 06560 Ankara, Turkey
2
Department of Biochemistry, Gazi University Faculty of Medicine, 06560 Ankara, Turkey
3
Department of Internal Medicine, Gazi University Faculty of Medicine, 06560 Ankara, Turkey
Correspondence should be addressed to Mehmet Muhittin Yalcin; yalcin.muhittin@gmail.com
Received 24 March 2016; Revised 20 June 2016; Accepted 2 August 2016
Academic Editor: Ed Randell
Copyright © 2016 Mehmet Muhittin Yalcin et al. Tis is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Aims. Growth Diferentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory
peptide for iron deposition. Current data is conficting about the relationship between hepcidin and disorders of glucose
metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in
nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose
tolerance (NGT). Methods. Tirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body
mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were signifcantly higher in IGT compared
to NGT. Tere were no diferences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We
found a positive correlation between GDF-15 and hepcidin levels. Tere were also positive correlations between GDF-15 and age,
uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the
multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions.
Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are
not signifcantly altered in prediabetic state.
1. Introduction
High iron concentrations have been suggested to be associ-
ated with subclinical infammation and increased oxidative
stress in type 2 diabetes mellitus (T2DM) [1]. Besides, a
positive association between fasting glucose and insulin
levels and chronic iron deposition has been reported in a
population study [2].
Hepcidin is a peptide hormone that regulates iron home-
ostasis in the body [3]. Hepcidin is synthesized from the
hepatocytes and causes negative efect on iron absorption and
cellular release via binding to ferroportin [3]. Alterations in
hepcidin levels have been reported in chronic diseases with
iron deposition [4, 5]. Tere are a growing number of studies
targeting the possible role of hepcidin in the pathogenesis
of insulin resistance and related diseases [6–8]. Decreased
or unchanged hepcidin concentrations have been found in
patients with polycystic ovary and metabolic syndrome [9–
11]. In patients with T2DM, some studies have reported
decreased circulating hepcidin levels while others showed no
change [10, 12, 13]. To the best of our knowledge, there is
no data regarding hepcidin concentrations in subjects with
impaired glucose tolerance.
Growth Diferentiation Factor-15 (GDF-15), which is also
known as macrophage inhibitory cytokine 1 (MIC-1), has
been suggested as one of the regulators of hepcidin [14].
GDF-15 is an anti-infammatory cytokine secreted mainly
from the macrophages in response to oxidative stress and
infammation [15]. Plasma GDF-15 levels have been found to
be positively correlated with abdominal obesity and insulin
resistance in obese subjects without diabetes [16]. Also,
increasing efect of hyperinsulinemia on circulating GDF-
15 concentrations has been shown in a clamp study [17].
Increased GDF-15 levels have been reported in patients with
Hindawi Publishing Corporation
Journal of Diabetes Research
Volume 2016, Article ID 1240843, 5 pages
http://dx.doi.org/10.1155/2016/1240843